The reasons why a specific subset of glioblastoma (GBM) patients survive longer than others is still unclear. This study analyzed a cohort of long-term and very-long-term GBM survivors to determine ...which genetic alterations or patient's characteristics influence survival time.
We retrospectively reviewed a cohort of GBM patients treated at our institution over the last 20 years, stratifying patients in three groups: those with a survival time ≥ 36 months and < 120 months (LTS), ≥120 months (VLTS), and < 36 months, respectively. Clinical (age, sex, focality, resection degree, Karnofsky performance status), and immunohistochemical and molecular data (Ki-67 expression and multiple genes alterations) were collected. We then utilized principal component analysis, logistic regression, and Cox proportional hazard models to identify those variables associated with survival.
Younger age at presentation (HR = 0.36, 95% CI 0.21–0.67, p = .001), and MGMT promoter (MGMTp), methylated, HR = 0.57, CI 0.34–0.96, p = .034) were associated with higher odds of VLTS survival. The multivariate analysis showed how the combination of younger age (< 50 years), Ki-67 < 10%, and the coexistence of TERTp not mutated, MGMTp methylated, and IDH1/2 mutated in the same patient are also associated with higher odds of survival (HR = 0.10, CI 0.01–0.74, p = .025).
We confirmed younger age at presentation and MGMTp methylation as the only independent factors associated with VLTS. The exceptional survival of our VLTS patients is probably associated with different, still understudied, gene mutations, or with the coexistence of multiple factors.
•younger age at presentation and MGMTp gene methylation are the only independent factors associated with prolonged survival•Is the coexistence of a specific pattern of mutations that had a positive benefit on survival•prolonged survival may be the results of an understudied gene mutation or a synergistic pattern of contributing factors
Abstract
BACKGROUND
Vestibular schwannoma extending to the fundus of the internal auditory canal is currently considered an unfavorable condition for hearing preservation surgery via a retrosigmoid ...approach because the lateral end of the canal is hard to view directly during microsurgery.
OBJECTIVE
To present an improved retrolabyrinthine meatotomy (RLM) technique that enables the full length of the cochlear and facial nerves to be inspected up to their orifices on the fundus. Long-term results are briefly reported.
METHODS
A consecutive series of 100 cases with various degrees of fundus involvement underwent surgery via a retrosigmoid approach and RLM. The follow-up ranged from 4 to 14 yr. Outcomes on hearing and facial nerve function were recorded, and preoperative MRI findings of the tumor on the fundus were correlated with the surgical findings and the long-term radicality of the tumor resection.
RESULTS
Residual tumor on the fundus was identified in 3 cases, all belonging to the group with tumors adhering to the fundus. The functional results were in line with the best reported outcomes of this surgery.
CONCLUSION
RLM via a retrosigmoid approach seemed adequate for the purposes of hearing preservation surgery and enabled the full course of the facial and cochlear nerves through the internal auditory canal to be exposed to direct view. Tumors adhering to the vestibular quadrant of the fundus were more difficult to remove, and there were a few cases of local residual tumor.
We report our preliminary experience concerning the use of thrombin-gelatin hemostatic matrix to strengthen the final hemostasis after posterior fossa low-grade tumor surgery in children. To our ...knowledge, this is the first report regarding the use of hemostatic matrix in pediatric neurosurgery.
Between 2012 and 2016, twenty-three patients underwent posterior fossa surgery for low-grade gliomas in our department. The mean age was 6.35 years; 12 patients were female and 11 male. Histology revealed pilocytic astrocytoma in 15 cases, ependymoma in 7 cases, and gangliocytoma in 1 case. At the end of the surgery, effective hemostasis was achieved using standard methods and, in order to strengthen the final hemostasis, we used a thrombin-gelatin hemostatic matrix. In all of the cases a postoperative MRI was performed within 24 after the surgery; during hospitalization the patients underwent a clinical evaluation. Moreover, blood samples were taken to evaluate inflammatory parameters, hemoglobin, and sodium, and kidney and liver tests were performed according to the standard protocol.
The postoperative MRI did not show any complications imputable to the matrix. Dur ing radiological and clinical follow-up none of the patients showed any delayed complications related to the matrix.
In our practice we found thrombin-gelatin hemostatic matrix sealant to be a valid and safe tool for strengthening hemostasis in pediatric low-grade posterior fossa surgery.
Abstract
The Astropy Project supports and fosters the development of open-source and openly developed
Python
packages that provide commonly needed functionality to the astronomical community. A key ...element of the Astropy Project is the core package
astropy
, which serves as the foundation for more specialized projects and packages. In this article, we provide an overview of the organization of the Astropy project and summarize key features in the core package, as of the recent major release, version 2.0. We then describe the project infrastructure designed to facilitate and support development for a broader ecosystem of interoperable packages. We conclude with a future outlook of planned new features and directions for the broader Astropy Project.
. Objectives: Cisplatin (cisPt) is used as a chemotherapeutic agent for the treatment of a variety of human tumours; more recently, it has been demonstrated that tumour cell exposure to cisPt ...ultimately results in apoptosis, but the mechanism by which nuclear cisPt/DNA generates the cytoplasmic cascade of events involved has not been clarified. We have investigated the effects of cisPt on proliferation in the neuronal cell line B50, with particular attention being given to understand whether mitochondria are a target of cisPt and their involvement in the apoptotic process. Materials and methods: Rat neuronal B50 cells were used to investigate the mechanisms of cisPt‐induced cytotoxicity; this line has been used as a model system for neurotoxicity in vivo. Results: Changes in proliferation, induction of apoptosis, activation of caspase‐3 and DNA fragmentation were observed in the cells, as well as morphological and biochemical alterations of mithocondria. Activation of caspase‐9 confirmed that mitochondria are a target of cisPt. Conclusion: CisPt exerts cytotoxic effects in the neuronal B50 cell line via a caspase‐dependent pathway with mitochondria being central relay stations.
Tractography of the facial nerve based on single-shell diffusion MR imaging is thought to be helpful before surgery for resection of vestibular schwannoma. However, this paradigm can be vitiated by ...the isotropic diffusion of the CSF, the convoluted path of the facial nerve, and its crossing with other bundles. Here we propose a multishell diffusion MR imaging acquisition scheme combined with probabilistic tractography that has the potential to provide a presurgical facial nerve reconstruction uncontaminated by such effects.
Five patients scheduled for vestibular schwannoma resection underwent multishell diffusion MR imaging (b-values = 0, 300, 1000, 2000 s/mm
). Facial nerve tractography was performed with a probabilistic algorithm and anatomic seeds located in the brain stem, cerebellopontine cistern, and internal auditory canal. A single-shell diffusion MR imaging (b-value = 0, 1000 s/mm
) subset was extrapolated from the multishell diffusion MR imaging data. The quality of the facial nerve reconstruction based on both multishell diffusion MR imaging and single-shell diffusion MR imaging sequences was assessed against intraoperative videos recorded during the operation.
Single-shell diffusion MR imaging-based tractography was characterized by failures in facial nerve tracking (2/5 cases) and inaccurate facial nerve reconstructions displaying false-positives and partial volume effects. In contrast, multishell diffusion MR imaging-based tractography provided accurate facial nerve reconstructions (4/5 cases), even in the presence of ostensibly complex patterns.
In comparison with single-shell diffusion MR imaging, the combination of multishell diffusion MR imaging-based tractography and probabilistic algorithms is a more valuable aid for surgeons before vestibular schwannoma resection, providing more accurate facial nerve reconstructions, which may ultimately improve the postsurgical patient's outcome.
The current treatment options for acoustic neuromas (AN) - observation, microsurgery and radiotherapy - should assure no additional morbidity on cranial nerves VII and VIII. Outcomes in terms of ...disease control and facial function are similar, while the main difference lies in hearing. From 2012 to 2016, 91 of 169 patients (54%) met inclusion criteria for the present study, being diagnosed with unilateral, sporadic, intrameatal or extrameatal AN up to 1 cm in the cerebello-pontine angle; the remaining 78 patients (46%) had larger AN and were all addressed to surgery. The treatment protocol for small AN included observation, translabyrinthine surgery, hearing preservation surgery (HPS) and radiotherapy. Hearing function was assessed according to the Tokyo classification and the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) classification. Sixty-one patients (71%) underwent observation, 19 (22%) HPS and 6 (7%) translabyrinthine surgery; 5 patients were lost to follow-up. Median follow-up was 25 months. In the observation group, 24.6% of patients abandoned the wait-and-see policy for an active treatment; the risk of switching from observation to active treatment was significant for tumour growth (p = 0.0035) at multivariate analysis. Hearing deteriorated in 28% of cases without correlation with tumour growth; the rate of hearing preservation for classes C-D was higher than for classes A-B (p = 0.032). Patients submitted to HPS maintained an overall preoperative hearing class of Tokyo and AAO-HNS in 63% and 68% of cases, respectively. Hearing preservation rate was significantly higher for patients presenting with preoperative favourable conditions (in-protocol) (p = 0.046). A multi-option management for small AN appeared to be an effective strategy in terms of hearing outcomes.
We examined the effects of the antitumor agent cisplatin on the development and plasticity of cerebellar cytoarchitecture. Since knowledge of the parallel and climbing fiber-Purkinje cell system is ...important in order to determine the architectural basis of cerebellar function, we used immunofluorescence for vesicular glutamate transporters (VGluT1 and VGluT2) to evaluate the trend of synaptogenesis of parallel and climbing fibers on Purkinje cells in the cerebellum vermis after a single injection of cisplatin to 10-day-old rats, i.e., during a crucial period of cerebellar development. The temporal and spatial patterns of VGluT1 and VGluT2 immunoreactivity after the early cisplatin injury provided evidence that remodeling of excitatory afferents and Purkinje cell dendrites occurs. After an early slow down of Purkinje cell dendrite growth, 7 days following the treatment, the extension of the molecular layer was reduced, as was parallel fiber innervation, but VGluT1 immunoreactive fibers contacted Purkinje cell dendrite branches extending within the external granular layer. VGluT2 immunopositive climbing fiber varicosities were still largely present on the soma and stem dendrites of Purkinje cells. Twenty days after the cisplatin injection, the thickness of the VGluT1 immunopositive molecular layer was reduced. VGluT2 climbing fiber varicosities were found on the remodeled Purkinje cell dendrites, as in controls, although at a lower density. Alterations in the immunoreactivity for polysialic acid neural cell adhesion molecule (PSA-NCAM) during the recovery phase suggest that this molecule plays a fundamental role not only during development, but also in the reorganization of neuroarchitecture. The changes were restricted to the neocerebellar vermis and were likely dependent on the different timing of lobule formation. The results of these investigations reveal the existence of vulnerability windows of the cerebellum to exposure to experimental or environmental cytotoxic agents during a critical period in development.
Disease prognosis is very poor in patients with brain tumors. Cognitive deficits due to disease or due to its treatment have an important weight on the quality of life of patients and caregivers. ...Studies often take into account quality of life as a fundamental element in the management of disease and interventions have been developed for cognitive rehabilitation of neuropsychological deficits with the aim of improving the quality of life and daily-life autonomy of patients. In this literature review, we will consider the published studies of cognitive rehabilitation over the past 20 years.
Introduction
Vagus nerve stimulation (VNS) is a neuromodulation technique approved for Treatment-Resistant Depression (TRD). Evidence regarding its long-term efficacy and safety is still scarce.
...Objectives
To descriptively report a case series of 3 patients undergoing adjunctive VNS for TRD with an over 10-year follow-up.
Methods
We investigated outcomes of clinical interest in patients with ongoing VNS for at least 10 years after the device implantation. They had participated in a larger single-arm interventional study conducted at the University Hospital of Padua. They were diagnosed with chronic unipolar (1), recurrent unipolar (1), and bipolar (1) TRD.
Results
Our 3 cases had an average 14-year history of psychiatric disease before surgery. Afterward, all subjects achieved clinical remission within two years. 2 patients experienced relapses within the first 4 years of treatment (respectively, 1 and 2 episodes). The other case showed a recurrent trend of brief relapses every two years. Only 1 individual needed to be admitted to the psychiatric unit once. None of them committed suicidal attempts. Prescription of antidepressants remained almost unchanged after the first two years. 2 individuals improved and 1 maintained their working position. Common adverse events were voice alteration (3/3), neck pain (2/3), and cough (2/3).
Conclusions
Very few cases of 10-year VNS for TRD have been reported so far. For our subjects, VNS was most likely to have a major impact on the clinical course of the disease. This treatment can be a safe and effective adjunctive intervention in a subgroup of patients with TRD.
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